title: Protein kinase Cβ2 inhibition reduces hyperglycemia-induced neural tube defects through suppression of a caspase 8-triggered apoptotic pathway.
abstract: OBJECTIVE
  Neural tube defects in diabetic embryopathy are associated with increased protein kinase C (PKC)β2 activity and programmed cell death (apoptosis). The apoptosis is triggered by caspase 8, which activates members of the Bcl-2 and caspase families, such as Bid and caspase 3. Whether PKCβ2 regulates caspase 8-induced apoptosis remains to be addressed.
  
  
  METHODS
  Mouse embryos at embryonic day 8.5 were cultured in a high concentration of glucose (22 mmol/L) and treated with PKCβ2 inhibitor (50 nmol/L) for 48 hours. The levels of apoptosis and activation of apoptotic factors were quantified using the terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling and Western blot assays, respectively.
  
  
  RESULTS
  Reduction in the rate of neural tube defect by PKCβ2 inhibition is associated with significant decreases in the levels of apoptosis, and caspase 8, caspase 3, and Bid activation, and cytochrome C release from mitochondria, to the similar levels as in euglycemic controls (8.3 mmol/L; P < .05).
  
  
  CONCLUSIONS
  PKCβ2 influences a caspase 8-regulated apoptotic pathway in diabetic embryopathy.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Yuanning
authors.initials: Y
authors.lastname: Cao
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zhao
authors.forename: Richard L
authors.initials: RL
authors.lastname: Eckert
authors.forename: E Albert
authors.initials: EA
authors.lastname: Reece
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D053181:Caspase 8 / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000187:drug effects; D006943:Hyperglycemia / Q000150:complications*; D051379:Mice; D009436:Neural Tube Defects / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D064546:Protein Kinase C beta; D047428:Protein Kinase Inhibitors / Q000494:pharmacology
chemical_list: D047428:Protein Kinase Inhibitors; D011493:Protein Kinase C; D064546:Protein Kinase C beta; C505526:Casp8 protein, mouse; D053181:Caspase 8